We will determine if the targeting of liposomes with bilayer situated carbohydrate ligands to a specific cell surface receptors in vivo enhance the intracellular delivery and bioavailability of liposome encapsulated agents. Three parallel approaches will be used to identify the unique properties of targeted liposomes that control the pharmacokinetics and cellular bioavailability of the encapsulated agent: (1) quantitation of the bioavailability and intracellular delivery of liposome encapsulated agents, including albumin. A double label technique will be utilized to determine the rate of intracellular delivery and breakdown of labelled albumin in the liver. Delivery at the cellular level (hepatocytes versus Kupffer cells) and distribution at the subcellular level will be quantitated by radioisotopic techniques following cell and subcellular fractionation. Comparison between surface ligands specific for each cell type and non-modified liposomes will be made. (2) The effectiveness of the encapsulated agent delivered to the liver will be examined using a chemical induced rat hepatoma model and a mouse colon carcinoma that metastasize to the liver. Comparison between targeted liposomes and non-targeted liposomes will be made. (3) Determinations of the parameters that control the disposition of liposomes with bilayer situated carbohydrates in vivo. The carbohydrates chosen for targeting include a lactosyl ceramide and a dimannosyldiglyceride. The parameters to be studied include vesicle size, lipid composition, surface density of the carbohydrate, length of the carbohydrate chain, and effect of putative inhibitors on liposome disposition.